GENETICS OF DRUG RESISTANCE AND PATHOGENIC MECHANISMS IN P FALCIPARUM MALARIA

寄生虫病实验室的疟疾遗传科对控制疟疾药物反应、发病机制和传播的因素进行基础研究。这项工作结合了连锁作图、野外人口调查、基因操作和基因产物分析等战略，以期发现基本的生物学信息，这些信息将用于开发新的诊断、治疗和控制措施。该部门的研究主要集中在恶性疟原虫上，这种寄生虫导致最严重的疟疾形式，每年导致200-300万人死于这种疾病。目前的项目包括1)抗药性的分子机制，特别是疟疾菌株对氯喹、奎宁和甲氟喹等关键抗寄生虫药物的抗药性；2)导致寄生红细胞抗原变异和免疫逃避的基因转录开关和DNA重组事件；3)非洲儿童中血红蛋白C和S(镰状细胞)的流行病学及其对严重疟疾的保护；4)12号染色体上对男性配子体发育产生不利影响的遗传缺陷。-疟疾；抗药性；抗原变异；血红蛋白；镰状细胞；氯喹；奎宁；甲氟喹；遗传学；基因组学-人类受试者和受试者：仅采访、问卷调查或调查

The Malaria Genetics Section of the Laboratory of Parasitic Diseases conducts basic research on factors that govern the drug response, pathogenesis and transmission of malaria. The work incorporates strategies of linkage mapping, field population surveys, gene manipulation and gene product analysis with a view toward the discovery of fundamental biological information that will be of use in the development of new diagnostics, therapeutics and control measures against the disease. The research of the section largely focuses upon Plasmodium falciparum, the parasite that causes the most severe form of malaria and produces 2-3 million deaths each year from the disease. Current projects include investigations of 1) molecular mechanisms of drug resistance, particularly the resistance of malaria strains to such crucial anti-parasite drugs as chloroquine, quinine, and mefloquine; 2) gene transcription switches and DNA recombination events responsible for the antigenic variation and immune evasion of parasitized red blood cells; 3) epidemiology of hemoglobins C and S (sickle-cell) and their protection against severe malaria in African children; 4) a genetic defect in chromosome 12 that adversely affects the development of male gametocytes. - malaria; drug resistance; antigenic variation; hemoglobins; sickle-cell; chloroquine; quinine; mefloquine; genetics; genomics - Human Subjects & Human Subjects: Interview, Questionaires, or Surveys Only